A 61-Year-Old Woman With Hepatocellular Carcinoma - Episode 6
Pierre Gholam, MD, discusses future directions and novel therapeutic agents for the treatment of unresectable HCC.
Pierre Gholam, MD: The treatment of unresectable HCC [hepatocellular carcinoma] has improved dramatically over the past 15 years. Given where we are today compared to even 3 years ago, I would say the improvement in outcomes and the wealth of options available to patients is expanding fairly rapidly. This obviously does not mean we do not have significant unmet needs. I think by far the biggest unmet need, which is holding this field from accelerating and benefiting patients even further, is the lack of an accurate and reliable biomarker for disease, disease burden specifically, and response to therapy. Until we find this, I think the field is going to continue to struggle with less-than-optimal end points for monitoring response to therapy and reliance on very hard end points like overall survival [OS], which are obviously very important, but are relatively insensitive to at least telling us whether a drug has potential over time or not, at least in the initial phases.
There may be missed opportunities for drug development because we do not have a good handle on a biomarker that reflects a burden, especially early in the course of drug development. There are plenty of treatment combinations being investigated at this point. These include the combination of TKIs [tyrosine kinase inhibitors] and immunotherapy primarily, but also combinations of immunotherapies together. We anticipate that these will mostly report in this coming calendar year. This should be a very interesting year to hear about the studies that are looking at, for example, durvalumab and tremelimumab, a combination of immunotherapies, cabozantinib and nivolumab, as well as other combinations that fit those patterns in the setting of first-line therapy. There are already data for lenvatinib and pembrolizumab, a combination of a TKI and an immunotherapy agent, which is well known and widely used.
There is a large study ongoing that we’ll hopefully report soon, but we already have some preliminary data from the phase 1b study reported by [Richard] Finn, [MD,] and colleagues last year. This study shows a promising efficacy trend in the combination, with a pretty good objective response rate and no dose-limiting toxicities, which is what led the investigators to initiate a larger phase 2b and transitioning to a phase 3 study. There is a very interesting study…out of Taiwan. This is a combination of Taiwanese patients from different hospitals and cancer centers, where they looked at a real-world setting of some patients getting lenvatinib versus lenvatinib plus pembrolizumab. This was presented at this year’s ASCO [American Society of Clinical Oncology] meeting. The OS and PFS [progression-free survival] data I think are worth looking at, but may be overly optimistic given the small size of the study. Nonetheless, they show that at least in these authors’ hands, lenvatinib plus pembrolizumab appeared to be, if you want to interpret the data accurately, vastly superior to lenvatinib alone when it came to some of these end points. I don’t believe they had a censored OS, and the median overall survival hadn’t been reached by the time they concluded the study.
These are promising data. I think ultimately the proof in whether these combinations come to fruition and expand our ability to treat patients will hopefully be evident, I’m fairly confident, no further than the next calendar year.
Transcript edited for clarity.
A 61-Year-Old Woman with Hepatocellular Carcinoma